The long-term objectives of this research program are to understand the structures of bone and dentin from the molecular to the micron level, in order to use these as a basis for addressing questions regarding the manner in which these tissues form, function and malfunction. The initial focus of the study is to better understand the fine structure of lamellar bone and intertubular dentin with particular emphasis on the organization of the crystals in the collagen fibrils. We will also investigate the crystal organization of peritubular dentin, and its structural relationship, if any, with intertubular dentin. In parallel we will apply our state-of-the-art technique for high resolution immunochemical mapping of antigens in vitrified tissue sections, to determine the locations of various NCP's in bone and dentin that are generally considered to be important in controlling mineralization. We feel that knowledge of their precise locations vis-a-vis the fine structure of the tissue, is one important key to assessing their functions. Structure and localization is also the basis for gaining insight into the malfunctioning of these tissues that occur in a variety of pathological problems. Comparison of the pathology with a normal control is a time-tested method for investigating the basis of the disease. The value of the comparison is a direct function of the quality of our knowledge of the control structure. Detailed comparisons of the structure of bones affected by osteogenesis imperfecta and osteoporosis, will be undertaken. Scanning electron microscopy of fractured surfaces, and transmission electron microscopy in the image and diffraction modes of heavily mineralized bone particles, lightly mineralized vitrified thin sections, as well as demineralized vitrified thin sections, are the major methods used in this research.